This prospective study of genetic prediabetics (including offspring of two diabetic parents and apparently unaffected monozygotic twins with a known diabetic twin-mate) moves into its 10th year. Over 500 study subjects (including 35 twins) have been evaluated metabolically at least once and approximately 350 are re-evaluated prospectively three times a year. Every 12 to 18 months, a standard 100 gm, Oral Glucose Tolerance Test is performed. In the interim visits, a variety of other tests including Cortisone-primed Oral Glucose, Intravenous Glucose, Intravenous Tolbutamide, Intravenous Glucagon, Oral Fructose, and a variety of other perturbations are performed. During all studies, blood glucose, serum insulin, serum growth hormone, serum cholesterol, and serum triglyceride are measured at appropriate intervals. An on-going population of healthy controls with no family history of diabetes are studied in parellel with the control group. A constant monitoring of the prevalence and incidence of chemical and overt diabetes in the population is made. In addition, a variety of statistical and discriminate function analyses are being performed continually in order to determine if there exists a reproducible, reasonably-easy measurable metabolic and/or hormonal defect that will serve as a marker for the predisposition to diabetes. Also under analysis is the relationship between the type and severity of diabetes in both parents and the prevalence and incidence of chemical and overt diabetes in the offspring, and the hormonal response to glucose in the "prediabetics" and chemical diabetics. BIBLIOGRAPHIC REFERENCES: Ganda, O.P., Kahn, C.B., Soeldner, J.S., and Gleason, R.E.: Dynamics of Tolbutamide, Glucose, and Insulin Interrelationships Following Varying Doses of Intravenous Tolbutamide in Normal Subjects. Diabetes 24:354-361, 1975. Johansen, K., Soeldner, J.S., Gleason, R.E., Gottlieb, M.S., Park, B.N., Kaufmann, R.L., and Tan M.H.: Serum Insulin and Growth Hormone Response Patterns in Monozygotic Twin Siblings of Patients with Juvenile-Onset Diabetes. N.E.J.M. 293:57-61, 1975.